The effect of heparin on antigen-induced mucus hypersecretion in the nasal epithelium of sensitized rats.

The effect of heparin on antigen-induced mucus hypersecretion in the nasal epithelium of sensitized rats.
复制标题

肝素对致敏大鼠鼻上皮抗原诱导的粘液分泌过多的影响。

DOI:
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发表时间:
2013
影响因子:
6.8
通讯作者:
Takeshi Shimizu
Takeshi Shimizu
中科院分区:
医学2区
文献类型:
--
作者:
T. Ogawa;S. Shimizu;Takeshi Shimizu

文献摘要

被引文献

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背景 肝素是治疗过敏性呼吸道炎症的潜在抗炎药物。为了阐明肝素在变态反应性炎症中的作用,我们观察了肝素对致敏大鼠鼻上皮抗原诱导的粘液高分泌和嗜酸性粒细胞和中性粒细胞渗入的影响。 方法 用卵清蛋白(OVA)鼻腔攻击致敏大鼠鼻腔上皮细胞,诱导杯状细胞肥大和化生改变。观察低分子肝素(LMWH,1-1000IU/0.1ml)滴鼻对大鼠鼻腔粘液产生及嗜酸性粒细胞/中性粒细胞浸润的影响。 结果 小剂量LMWH(1-10IU/0.1ml)可刺激OVA致敏大鼠鼻上皮黏液产生,100IU/0.1mlLMWH对OVA致敏大鼠鼻上皮黏液产生无明显影响。鼻腔滴入大剂量低分子肝素(1000IU/0.1ml)可显著抑制OVA诱导的粘液产生。鼻腔滴注低分子肝素(1-1000IU/0.1ml)可剂量依赖性地抑制嗜酸性粒细胞和中性粒细胞向鼻黏膜的渗透。 结论 这些结果表明,肝素对变态反应性炎症的粘液高分泌和嗜酸性粒细胞和中性粒细胞的渗透有抑制作用,而大剂量肝素对粘液的产生有抑制作用。大剂量肝素鼻腔滴注为鼻变应性炎症的治疗提供了一种新的治疗策略。
BACKGROUND Heparin is a potential anti-inflammatory drug for allergic airway inflammation. To elucidate the effects of heparin on allergic inflammation, we examined the in vivo effects of heparin on antigen-induced mucus hypersecretion and infiltration of eosinophils and neutrophils in the nasal epithelium of sensitized rats. METHODS We induced hypertrophic and metaplastic changes of goblet cells in the nasal epithelium of ovalbumin (OVA)-sensitized rats by intranasal challenge with OVA. The effects of intranasal instillation with low molecular weight heparin (LMWH; 1-1000IU/0.1ml) on mucus production and eosinophil/neutrophil infiltration were examined. RESULTS Intranasal instillation with low-dose LMWH (1-10IU/0.1ml) at 30 minutes before OVA instillation stimulated OVA-induced mucus production in the nasal epithelium of sensitized rats, whereas treatment with 100IU/0.1ml LMWH showed no effect. Intranasal instillation with high-dose LMWH (1000IU/0.1ml) significantly inhibited OVA-induced mucus production. Intranasal instillation with LMWH (1-1000IU/0.1ml) dose-dependently inhibited eosinophil and neutrophil infiltration into the rat nasal mucosa. CONCLUSIONS These results indicate that heparin inhibits mucus hypersecretion and infiltration of eosinophils and neutrophils in allergic inflammation, though the inhibitory effect against mucus production is obtained in high-dose heparin. Intranasal instillation with high-dose heparin may provide a new therapeutic strategy for the treatment of nasal allergic inflammation.